Methamphetamine, in large doses, was administered to rats for 30 hours and the effect on biogenic metabolism was monitored. Tyrosine hydroxylase activity was depressed in the neostriatum and substantia nigra. This effect was prevented with concomitant administration of GABA transaminase inhibitors. Tyrosine hydroxylase activity was also monitored in mesolimbic areas of the brain and correlated with dopamine levels. The kinetic characteristics of striatal tyrosine hydroxylase activity after administration of the methamphetamine are under investigation.